White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids—lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.

BackgroundThe marine n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to improve treatment of type 2 diabetic (T2D) patients remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA + DHA and the insulin-sensitizing drug pioglitazone in overweight/obese T2D patients already treated with metformin.MethodsIn a parallel-group, four-arm, randomized trial, 69 patients (66 % men) were assigned to 24-week-intervention using: (i) corn oil (5 g/day; Placebo), (ii) pioglitazone (15 mg/day; Pio), (iii) EPA + DHA concentrate (5 g/day, containing ~2.8 g EPA + DHA; Omega-3), or (iv) pioglitazone and EPA + DHA concentrate (Pio& Omega-3). Data from 60 patients were used for the final evaluation. At baseline and after intervention, various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures, EPA + DHA content in serum phospholipids was evaluated using shotgun lipidomics and mass spectrometry, and hyperinsulinemic-euglycemic clamp and meal test were also performed. Indirect calorimetry was conducted after the intervention. Primary endpoints were changes from baseline in insulin sensitivity evaluated using hyperinsulinemic-euglycemic clamp and in serum triacylglycerol concentrations in fasting state. Secondary endpoints included changes in fasting glycemia and glycated hemoglobin (HbA1c), changes in postprandial glucose, free fatty acid and triacylglycerol concentrations, metabolic flexibility assessed by indirect calorimetry, and inflammatory markers.ResultsOmega-3 and Pio& Omega-3 increased EPA + DHA content in serum phospholipids. Pio and Pio& Omega-3 increased body weight and adiponectin levels. Both fasting glycemia and HbA1c were increased by Omega-3, but were unchanged by Pio& Omega-3. Insulin sensitivity was not affected by Omega-3, while it was improved by Pio& Omega-3. Fasting triacylglycerol concentrations and inflammatory markers were not significantly affected by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by Pio& Omega-3.ConclusionBesides preventing a modest negative effect of n-3 fatty acids on glycemic control, the combination of pioglitazone and EPA + DHA can be used to improve lipid metabolism in T2D patients on stable metformin therapy.Trial registrationEudraCT number 2009-011106-42.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-015-0047-9) contains supplementary material, which is available to authorized users.

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It has been shown that it is possible to modify macronutrient oxidation, physical fitness and resting energy expenditure (REE) by changes in diet composition. Furthermore, mitochondrial oxidation can be significantly increased by a diet with a low glycemic index. The purpose of our trial was to compare the effects of a vegetarian (V) and conventional diet (C) with the same caloric restriction (−500 kcal/day) on physical fitness and REE after 12 weeks of diet plus aerobic exercise in 74 patients with type 2 diabetes (T2D). An open, parallel, randomized study design was used. All meals were provided for the whole study duration. An individualized exercise program was prescribed to the participants and was conducted under supervision. Physical fitness was measured by spiroergometry and indirect calorimetry was performed at the start and after 12 weeks Repeated-measures ANOVA (Analysis of variance) models with between-subject (group) and within-subject (time) factors and interactions were used for evaluation of the relationships between continuous variables and factors. Maximal oxygen consumption (VO2max) increased by 12% in vegetarian group (V) (F = 13.1, p < 0.001, partial η2 = 0.171), whereas no significant change was observed in C (F = 0.7, p = 0.667; group × time F = 9.3, p = 0.004, partial η2 = 0.209). Maximal performance (Watt max) increased by 21% in V (F = 8.3, p < 0.001, partial η2 = 0.192), whereas it did not change in C (F = 1.0, p = 0.334; group × time F = 4.2, p = 0.048, partial η2 = 0.116). Our results indicate that V leads more effectively to improvement in physical fitness than C after aerobic exercise program.

Background & aims: Reward circuitry in the brain plays a key role in weight regulation. We tested the effects of a plant-based meal on these brain regions. Methods: A randomized crossover design was used to test the effects of two energy-and macronutrientmatched meals: a vegan (V-meal) and a conventional meat (M-meal) on brain activity, gastrointestinal hormones, and satiety in participants with type 2 diabetes (T2D; n ¼ 20), overweight/obese participants (O; n ¼ 20), and healthy controls (H; n ¼ 20). Brain perfusion was measured, using arterial spin labeling functional brain imaging; satiety was assessed using a visual analogue scale; and plasma concentrations of gut hormones were determined at 0 and 180 min. Repeated-measures ANOVA was used for statistical analysis. Bonferroni correction for multiple comparisons was applied. The Hedge's g statistic was used to measure the effect size for means of paired difference between the times (180-0 min) and meal types (MÀV meal) for each group. Results: Thalamus perfusion was the highest in patients with T2D and the lowest in overweight/obese individuals (p ¼ 0.001). Thalamus perfusion decreased significantly after ingestion of the M-meal in men with T2D (p ¼ 0.04) and overweight/obese men (p ¼ 0.004), and it decreased significantly after ingestion of the V-meal in healthy controls (p < 0.001; Group x Meal x Time: F ¼ 3.4; p ¼ 0.035). The effect size was À0.41 (95% CI, À1.14 to 0.31; p ¼ 0.26) for men with diabetes; À0.72 (95% CI, À1.48 to 0.01; p ¼ 0.05) for overweight/obese men; and 0.82 (95% CI, 0.09 to 1.59; p ¼ 0.03) for healthy men. Postprandial secretion of active GLP-1 increased after the V-meal compared with the M-meal by 42% (95% CI 25e62%; p ¼ 0.003) in men with T2D and by 41% (95% CI 24e61%; p ¼ 0.002) in healthy controls. Changes in thalamus perfusion after ingestion of both test meals correlated with changes in satiety (r ¼ þ0.68; p < 0.01), fasting plasma insulin (r ¼ þ0.40; p < 0.01), C-peptide (r ¼ þ0.48; p < 0.01) and amylin (r ¼ þ0.55; p < 0.01), and insulin secretion at 5 mmol/l (r ¼ þ0.77; p < 0.05). Conclusions: The higher postprandial GLP-1 secretion after the V-meal in men with T2D, with concomitant greater satiety and changes in thalamus perfusion, suggest a potential use of plant-based meals in addressing the key pathophysiologic mechanisms of food intake regulation. Trial registration ClinicalTrials.gov number, NCT02474147.